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2018/08/09
Pain Management ‐ Cur Pers ‐ CMT ‐HANDOUT ‐ AUGUST 2018 1
Pain ManagementCurrent perspectives
Helgard Meyer, FCFP(SA)Department of Family Medicine
University of PretoriaWilgers MR Medical Centre
Cost of painPainter in J Clin Rheum, 2013
Back pain alone is estimated to cost
$125 billion annually
Updating the definition of painWilliams et al in Pain, 2016
“Pain is a distressing experience associated with actual or potential tissue
damage with sensory, emotional, cognitive, and social components.”
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Pain Management ‐ Cur Pers ‐ CMT ‐HANDOUT ‐ AUGUST 2018 2
Acute painHoldcroft in Core topics in Pain, 2005
Normal biological response
Protects / promotes healing
Unrelieved acute pain:
catecholamines
heart rate
Shallow breathing
Shock
Delayed healing
Nervous system effects
May evolve into chronic pain
Must be treated and its cause be removed
Peripheral sensitizationWoolf in Pain, 1986
Central sensitizationWoolf in Rheum Dis Clin, 2002
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Pain Management ‐ Cur Pers ‐ CMT ‐HANDOUT ‐ AUGUST 2018 3
Chronic painHoldcroft in Core topics in Pain, 2005
Persists longer than the expected time for healing (>3 months)
No “warning” function
Underlying disease may be absent
Pain becomes the “disease”
Emotional / psychosocial factors important
Complex to treat
Interdisciplinary approach
Management vs eradication
Results in the strongest analgesics for the wrong patients.
‘Higher pain intensity in chronic musculo‐skeletal pain mostly indicates
more emotional and psychosocial factors.”
WarningFocussing only on pain intensity in the assessment of chronic pain patients
Sullivan in Pain, 2016
Assessment of patients in chronic painMackichan in Rheum Dis Clin North Am, 2008
Meyer in SA Fam Pract, 2011
Personal report
Subjective (PQRST)
Measure
Unique and personal experience
DN4
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Pain Management ‐ Cur Pers ‐ CMT ‐HANDOUT ‐ AUGUST 2018 4
Treatment goals for chronic pain patientsAshburn in Lancet, 1999
Meyer in SA Fam Pract, 2007
Reduction of pain (30% is clinically significant)
Improvement in co‐morbidities (e.g. mood and sleep)
Improve patient’s functioning
Return to work
Chronic pain – multimodal approach
Pharmacotherapy
Assessment of patient
Physical therapy Supervised exercise
Education
Behavioural therapyOccupational therapy
MORE
PharmacotherapyGronow in Anaes and Int Care, 2010
Primary analgesics
Paracetamol
NSAID’s / COX‐2 inhibitorsIbuprofenDiclofenacNaproxenCelecoxibEtoricoxib, etc
Opioids
MildCodeineTramadol
Strong:MorphineHydromorphoneBuprenorphineOxycodoneFentanylTapentadol
Adjuvant analgesics
TricyclicsAmitriptyline, Cyclobenzaprine
SNRI’sDuloxetine, etc.
Anticonvulsants:CarbamazepineGabapentinPregabalin
Local anaesthetics
Diverse analgesicsKetamineCannabinoidsMuscle relaxants
Topical analgesicsLidocaine patch
Capsaicin patch
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Pain Management ‐ Cur Pers ‐ CMT ‐HANDOUT ‐ AUGUST 2018 5
Non‐opioid analgesicsParacetamol
NSAIDsCOX‐2 inhib
STEP 1Weak opioids
CodeineTramadol
STEP 2Strong opioids
STEP 3Nerve blockEpiduralsPCA pump
STEP 4
New adaptation of the analgesic ladderVargas‐Schaffer in Can Fam Phys, 2010
Chronic cancer and non‐cancer pain
NSAIDs(with or without
adjuvantsat each step)
Acute painChronic pain without controlAcute flare‐up of chronic pain
Low back painCancer pain
etc
NOCICEPTIVE PAINTissue damage activates
nociceptors e.g. osteo‐arthritis
surgery
NEUROPATHIC PAINLesion or disease of nervous system
Symptoms:NumbnessParaesthesiaHyperalgesiaElectric‐shocksBurning, etc
Mixed painBoth types of painco‐exist
IDIOPATHIC
Mechanism‐based pain classificationWoolf in Ann Int Med, 2009
Neuropathic pain
Disease / lesion of the somato‐sensory nervous system
Diabetic polyneuropathy
Post herpetic neuralgia
HIV neuropathy
Trigeminal neuralgia
Low back pain
Chronic post‐surgery pain (CPSP)
Mechanical compression
Post‐injury (CRPS)
Cancer
Chemotherapy
Amputation (“Phantom pain”)
Price in Clin J of Pain, 2004Management of Pain. Philadelphia, 2006
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Pain Management ‐ Cur Pers ‐ CMT ‐HANDOUT ‐ AUGUST 2018 6
Score > 4/10
Specificity: 90%Sensitivity: 83%
Bouhassira et al Pain, 2005.
Douleur Neuropathique 4
*
Pharmacotherapy in chronic neuropathic pain Dworkin et al in Pain, 2007
Tramadol
Severe pain
Acute flare‐up
Antidepressants
Tricyclics (amitriptyline)
SNRI’s (duloxetine)
α2‐ ligands Pregabalin
Gabapentin
First line
Second line
Strong opioids
Very careful patient selection
Cannabinoids
Third line
Algorithm for osteoarthritis of kneeBriyere et al in Sem Arthr Rheum, 2014
Step 1: Core set
Information / education
Weightloss
Exercise (aerobic, strengthening)
Combinations of treatment
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Pain Management ‐ Cur Pers ‐ CMT ‐HANDOUT ‐ AUGUST 2018 7
Algorithm for osteoarthritis of kneeBriyere et al in Sem Arthr Rheum, 2014
Step 2: Background treatment
Paracetamolor
Chronic SYSADOA(Symptomatic Slow‐acting
Drugs for Osteo‐arthritis)
Glucosamine‐sulphate Chondroitin‐sulphate
Still symptomatic: Add
Topical NSAIDSTopical capsaicin
Refer to physio for assessment(e.g. mal‐alignment)
Algorithm for osteoarthritis of kneeBriyere et al in Sem Arthr Rheum, 2014
Step 3: Advanced pharmacological management
Oral NSAIDS / COXIBS (Intermittently)
Increased GI risk:Avoid non‐selective NSAIDSCOX‐2 selective NSAIDS (±PPI)
Increased CV risk:Prefer naproxen
Increased renal risk:Avoid NSAIDS
Intra‐articular hyaluronateIntra‐articular corticosteroid
Algorithm for osteoarthritis of the kneeBriyere et al in Sem Arthr Rheum, 2014
Short‐term tramadolDuloxetine
Joint replacement surgery
Strong opioid analgesics (NB: guidelines)“Last resort”
End‐stage disease
If contra‐indicated
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Pain Management ‐ Cur Pers ‐ CMT ‐HANDOUT ‐ AUGUST 2018 8
ParacetamolNikles in Am J Ther, 2005Schug in Clin Rheum, 2006Nikles in Am J Ther, 2005Schug in Clin Rheum, 2006
Central effect?
COX‐2 inhibition (central prostaglandins)
Serotonergic anti‐nociceptive
NMDA receptor (via NO)
Cannabinoid receptors
Proven synergy
NSAIDs
Tramadol
Opioids
TramadolCicero et al in Drug Alcohol Dep, 1999
Schug in Anaesth Int Care, 2000Epstein et al in Biol Psych, 2006
Rafa in J Clin Pharm, 2008Barkin in Am J Therap, 2008Park et al in Clin Rheum, 2012Smith et al in Drug Eval, 2013
Central acting atypical opioid
Both mono‐aminergic and opioid effects
Also NMDA antagonist activity
Much less opioid receptor affinity than morphine
Very low abuse potential (< 1/100 000)
TramadolSchug in Anaesth Int Care, 2000Epstein et al in Biol Psych, 2006
Rafa in J Clin Pharm, 2008Barkin in Am J Therap, 2008Park et al in Clin Rheum, 2012Smith et al in Drug Eval, 2013
Pro‐drug (CYP2‐D‐6)
Adverse effects (serotonergic)
Nausea, vomiting
Dizziness, headache, sweating
Lowers convulsion threshold
Serotonin syndrome (very rare)
ModulationDNIC
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Pain Management ‐ Cur Pers ‐ CMT ‐HANDOUT ‐ AUGUST 2018 9
Analgesic combinationsSchug in Clin Rheum, 2006
Rational combinations:
Different receptors / mechanisms
Improved efficacy (NNT)
Reduced individual dosages
Less side effects
NB in mixed pain states
Clinical diagnosis
Neuromuscular:
Tremor, shivering
Autonomic:
Tachycardia, mydriasis
Mental:
Anxious, agitation
Serotonin syndromeBoyer et al in New Eng J Med, 2005
Backley et al in BMJ, 2014www.drugs.com (±1000 drugs)
Hyper‐reflexia, ankle clonus, ocular clonus
Sweating, hyperthermia
Confusion, delirium
Short term use for acute pain
End‐of‐life pain
High potency opioids in chronic painEvans in Best Practice, 2000
Russell in Pain Medicine, 2002
Niesch et al in Cochrane Rev, 2009
Noble et al in Cochrane Rev, 2010
Chronic non‐cancer pain – controversial
Morphine sulphate
Fentanyl
Oxycodone, etc
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Pain Management ‐ Cur Pers ‐ CMT ‐HANDOUT ‐ AUGUST 2018 10
“… appropriate and very careful patient
selection and follow‐up is paramount …”
Opioid risk assessment
Psycho‐social assessment
SA Guidelines for long term high potency opioid therapy in chronic non‐cancer pain
Raff et al in SAMJ, 2014 (Suppl)
Respiratory depression
Nausea, vomiting
Constipation
Bladder dysfunction
Pruritus
Tolerance / dependence / addiction
Endocrinological e.g. testosterone and libido
Opioid induced hyperalgesia
Adverse effects of opioid therapyRaff et al in SAMJ, 2014
Chronic widespread painGran in Res Clin Rheum, 2003
Yunus in Best Pract Rheum, 2007
±10‐12% of general population
Mostly musculo‐skeletal
Mostly a spectrum of disorders
Psychiatric disorders
Rheumatic disorders
Pain disorders
Sleep disorders
Fibromyalgia in 30‐40% of patients with CWP
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Pain Management ‐ Cur Pers ‐ CMT ‐HANDOUT ‐ AUGUST 2018 11
Other causes of chronic widespread painDaoud et al in Curr Pain and Headache Rep, 2002
Gerwin in J of Musc Skel Pain, 2004
Psychiatric disorders Mood disorders Somatoform pain disorders Unresolved emotional issues (chronic anger)
Hormonal / Metabolic Hypothyroidism Hyperparathyroidism Type 2 diabetis mellitus Iron deficiency Vit D deficiency
Infections HIV Tuberculosis “Brucellosis”
Drugs Opioid induced hyperalgesia (including OTC’s) Statins ARV’s Antipsychotics
Neoplastics conditions Myeloma Metastatic breast cancer etc.
Spondyloarthritis Ankylosing spondylitis Reactive arthritis Psoriatic arthritis, etc.
Sleep disorders Primary insomnia Obstructive sleep apnoea Restless legs syndrome
Chronic fatigue syndrome
Statin‐induced myalgiaThompson et al in JAMA, 2003Joy et al in Ann Int Med, 2009
Up to 10% of patients on statins (rhabdomyolysis rare)
Often long lag period
Often generalized myalgia
(More severe in hip‐ and shoulder girdles)
Intensity varies
Risk factors
Family history Physically very active
Females Alcohol
Low BMI Grapefruit
1990 ACR classification criteria for FMSWoolfe et al in Arthr Rheum, 1990
Widespread musculoskeletal pain > 3 months in all 4 quadrants
> 11/18 painful tender points with digital pressure of 4kg/cm2
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Pain Management ‐ Cur Pers ‐ CMT ‐HANDOUT ‐ AUGUST 2018 12
2010 ACR diagnostic criteria for FMSWolfe et al in Arth Care Res, 2010
Widespread Pain Index (WPI)
19 body areas
Symptom Severity Scale (SS)
Fatigue: 0‐3
Sleep: 0‐3
Cognitive: 0‐3
Somatic symptoms: 0‐3
Diagnostic
WPI > 7 SS > 5
WPI 3‐6 SS > 9
At least 3 months
Canadian guidelines for diagnosisand management of FMS
Canadian Guidelines for FMS in Rheum Arthr, 2013Fitzcharles et al in Pain Res Manag, 2013
Recognized as a valid pain syndrome based on recent neurophysiological evidence
Paradigm shift in diagnosis:
Diagnose and manage most “concentrated” in primary care
Do not “over‐investigate”
Not “all‐or‐nothing” phenomenon (“fibromyalgia‐ness”)
Emphasis on non‐pharmacological strategies
Diagnosis of FMSClauw in Am J of Med, 2009
Canadian Guidelines for FMS in Rheum Arthr, 2013Clauw in JAMA, 2014
Physical examination (“mandatory”)
Exclude other causes of widespread MSK pain
Detect peripheral pain generators
NB: Soft tissue pressure tenderness
Blood tests:
“Excessive testing contributes to uncertainty and fear and worsens prognoses”
FBC/ESR
CRP
TSH/T4
Creatinekinase (CK)
25‐OH‐D
Calcium
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Pain Management ‐ Cur Pers ‐ CMT ‐HANDOUT ‐ AUGUST 2018 13
Peripheral pain generators in FMSBorg‐Stein J in Rheum Dis Clin N Am, 2002Meyer in Curr Pain Headache Rep, 2002
Bennett in Rheum Dis Clin North Am, 2002Ablin et al in Joint Bone Spine, 2008
Clauw in J Clin Psych, 2008Giamberardino in IASP Clin Updates, 2008Gerwin in Phys Med Rehab Clin N Am, 2014
Headaches
Tendonitis
Surgery
Myofascial trigger points
Osteo‐arthritis
Endometriosis
Disc herniation
Treatment of FMSNon‐Medication
Goldenberg in JAMA, 2004Pooks in Curr Opin Rheum, 2007Clauw in J of Clin Rheum, 2007
Non‐pharmacological
Strong evidence
Patient education
Cognitive behavioral therapy
Multimodal approach
Cardiovascular exercise
Pharmacological
Modest evidence
Pregabalin
Duloxetine
Amitriptyline
Cyclobenzaprine
Tramadol ± paracetamol
} FDA approved
Cannabinoids for treatment of chronic non‐cancer pain;
a systematic review of randomized trialsLynch et al in British J of Clin Pharm, 2012
20 recent good quality randomized trials:
Cannabinoids are modestly effective and a safe treatment option for
chronic non‐cancer (predominantly neuropathic) pain.
Smoked cannabis effective in HIV‐neuropathy
Some evidence in FM and RA
Evidence base is growing
Need more long‐term studies
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